The conformations of peptides in phospholipid vesicles will be investigated by nuclear magnetic resonance and circular dichroism. Studies of membrane protein secondary structure should elucidate the organization of enzyme and structural proteins in membranes and eventually yield useful information on cell surface architecture. This work will focus primarily on the structures of bacteriorhodopsin and band III (the anion transport protein of human erythrocytes). Utilizing specific labels and synthetic oligopeptide fragments containing substrate binding sites, either isolated or recombined into intact protein, details of the geometry of the active site will be examined. Perturbations in conformations and overall secondary structures upon binding of substrates and inhibitors may elucidate mechanisms of action. In addition, the orientation of the protein and location of the active site, N- and C- termini, and other portions of the molecule will be determined using para magnetic probes. Finally, the secondary structure of these proteins will be examined to ascertain if membrane-embedded proteins differ in conformation from those in aqueous solution, and, if so, in what manner. This may provide a means of defining the unique structural features which permit certain proteins to anchor in the lipid matrices of cell membranes. These spectroscopic studies are intended to provide high resolution information concerning the active site conformation, molecular orientation changes with physiological effectors, and modes of protein folding in the hydrophobic environment of the membrane.